Locating marker/tracer elements detectable by neutron activated analysis within or on carrier microspheres, including microspheres used in biological experimentation

Abstract

Microspheres are permanently marked with non-radioactive stable isotopes of elements suitably detected by neutron activation analysis. The marked microspheres are suitable to permanently label diverse things. For example, families of stable-multiple-isotope-marked microspheres injected into an animal become lodged by the circulating blood within selected tissues of an animal during blood flow analysis experimentation. Absolute and relative abundances of these stable-isotope-marked microspheres residing within harvested tissues are readily accurately automatically measured in situ within the harvested tissue samples by neutron activation analysis. The quantitatively measured abundance of the isotopes, and associated microspheres, are accurately indicative of the former flow of blood containing the microspheres to the tissue. Microspheres are preferably marked with stable isotopes of gold, antimony, lanthanum, samarium, europium, terbium, holmium, ytterbium, lutetium, hafnium, tantalum, tungsten, rhenium, osmium, iridium, scandium and/or bromide.

What is claimed is:  
     
       1. A microsphere comprising: 
       a uniform plastic body in the form of a microsphere  
       marked with a predetermined amount of a non-radioactive stable isotope of an element which isotope and element can be rendered radioactive for detection by neutron activation analysis.  
     
     
       2. The marked microsphere according to claim  1   
       wherein the plastic body in the form of the microsphere physically holds the element;  
       wherein the marking is by physical association between the element and the microsphere.  
     
     
       3. The marked microsphere according to claim  1   
       wherein the plastic body in the form of the microsphere chemically binds the element;  
       wherein the marking is by chemical association between the element and the microsphere.  
     
     
       4. The marked microsphere according to claim  1   
       wherein the plastic body in the form of the microsphere is marked with a plurality of non-radioactive stable isotopes.  
     
     
       5. The marked microsphere according to claim  1  deployed within a sample wherein the plastic body in the form of a microsphere is marked with an isotope that is so rare within material of the sample that essentially all detection counts during neutron activation analysis can be attributed to presence of the isotope, and essentially none result from the material of the sample. 
     
     
       6. The marked microsphere according to claim  1  marked with a plurality of isotopes that, following neutron activation analysis, are by their unique energy signatures upon decay from an excited state individually distinguishable from one another. 
     
     
       7. The marked microsphere according to claim  1  marked with an isotope that, following neutron activation analysis, produces a daughter nuclide having a half life (t ½ ) greater than one day. 
     
     
       8. The marked microsphere according to claim  1  marked with an isotope that, following neutron activation analysis, produces a daughter nuclide having a half life (t ½ ) less than two years. 
     
     
       9. The marked microsphere according to claim  1  marked with an isotope that, following neutron activation analysis, produces a daughter nuclide having a half life (t ½ ) of at least two days and shorter than one month. 
     
     
       10. The marked microsphere according to claim  1  marked with an element from the group consisting of 
       gold, antimony, lanthanum, samarium, europium, terbium, holmium, ytterbium, lutetium, hafnium, tantalum, tungsten, rhenium, osmium, iridium, scandium and bromide.  
     
     
       11. The marked microsphere according to claim  1  color coded in accordance with the element with which it is marked. 
     
     
       12. The marked microsphere according to claim  1  used in blood flow analysis, the marked microsphere characterized in that it may be detected within a tissue sample resultant from blood flow analysis. 
     
     
       13. The marked microsphere according to claim  1  used in high-throughput screening for drug discovery and evaluation, the marked microsphere characterized in that it may be detected within a sample suitable for said high-throughput screening for drug discovery and evaluation. 
     
     
       14. The marked microsphere according to claim  1  comprising: 
       a biodegradable microsphere body; with which is associated  
       the non-radioactive stable isotope of an element only during the perpetuation of the physical microsphere body, the isotope being loosed when the body biodegrades.  
     
     
       15. The marked microsphere according to claim  14  wherein the biodegradable microsphere body consists essentially of a substance digestible in the gut of a higher animal. 
     
     
       16. The marked microsphere according to claim  1  wherein the plastic body in the form of the microsphere comprises: 
       polystyrene.  
     
     
       17. The marked microsphere according to claim  1  wherein the plastic body is uniformly homogeneously marked. 
     
     
       18. The marked microsphere according to claim  17  wherein the spherical plastic body comprises: 
       polystyrene.  
     
     
       19. A microsphere marked with a non-radioactive stable isotope of an element, 
       which isotope and element can be rendered radioactive for detection by neutron activation analysis,  
       wherein the isotope following neutron activation will generate a theoretical specific activity (s) of which exceeds 1×10 10  disintegrations per minute per kilogram of tracer, as appears in the equation for specific activity, s, induced in any parent nuclide during neutron activation:  
       
         
           s=6.02×10 26 φσfA −1 (0.5) t     1     /t     ½   [1−(0.5) t/     ½   ] 
         
       
       where: s=specific activity in disintegrations per unit mass (s −1 kg −1 ), φ=flux of neutrons in m −2 s −1 , σ=cross-section for neutron interaction with parent nuclide (m 2 ), f=fractional abundance of the parent nuclide, A=atomic weight of the parent element, t 1 =time between activation and counting (hours), t=activation period (hours), t ½ =half-life of daughter nuclide (hours). 
     
     
       20. The marked microsphere according to claim  19  comprising: 
       a spherical plastic body.  
     
     
       21. A microsphere comprising: 
       a uniform plastic body in the form of a microsphere  
       uniformly homogeneously marked with a predetermined amount of a non-radioactive stable isotope of an element which isotope and element can be rendered radioactive for detection by neutron activation analysis.  
     
     
       22. A microsphere marked with a non-radioactive stable isotope of an element the presence of which isotope which can be detected by neutron activation analysis, 
       the isotope following neutron activation generating a theoretical specific activity (s) of which exceeds 1×10 10  disintegrations per minute per kilogram of tracer, as appears in the equation for specific activity, s, induced in any parent nuclide during neutron activation:  
       
         
           s=6.02×10 26 φσfA −1 (0.5) t     1     /t     ½   [1−(0.5) t/t     ½   ] 
         
       
       where: s=specific activity in disintegrations per unit mass (s− 1 kg −1 ), φ=flux of neutrons in m −2 s −1 , σ=cross-section for neutron interaction with parent nuclide (m 2 ) f=fractional abundance of the parent nuclide, A=atomic weight of the parent element, t 1 =time between activation and counting (hours), t=activation period (hours), t ½ =half-life of daughter nuclide (hours).